Block 1 091212 Dna Mutations And Repairs

Front 1

What is the difference between transition and transversion?

Back 1

transition= single base location that replaces a purine with another purine or a pyrimidine with another pyrimidine
Transversion= point mutation where a purine is switched with a pyrmidine or a pyrimidine is switched with a purine

Front 2

What are 3 possible function effects produced by a single base substitution?

Back 2

1. Missense=Alters codon so changes AA in protein
2. Nonsense=Alters codon and creates a stop codon
3. Silent=alters codon but there is no change is the AA sequence

Front 3

What are 2 types of mutations that can produce frameshifts?

Back 3

1. Insertion
2. Deletion

Front 4

What are in-frame mutations?

Back 4

insertion or deletion of 3 base pairs

Front 5

What is the #1 form of inherited mental retardation?

Back 5

Fragile X syndrome= over methylation of tandem repeated DNA (>230 CGG repeats)

Front 6

What causes Huntington's disease?

Back 6

expansion of CAG repeats (>40)

Front 7

What is the mechanism for inserting triplet repeats?

Back 7

1.extra loop of CAP repeats insert into daughter strand during transcription and form a loop which normally is removed, if not removed it will become a template strand

Front 8

What are 3 types of DNA mutations?

Back 8

1. single base substitution
2. tandem repeated DNA
3. deletion and insertion

Front 9

What are 2 causes of DNA mutation?

Back 9

1. spontaneous
2. environmental

Front 10

How does tautomerization of bases cause transitions?

Back 10

tautomerization causes base pairing errors that generate substituation following a round of replication ex) normal = C-G, abbynormal= C-tautomerized A

Front 11

What type of mutation can result from deamination of cytosine?

Back 11

If cytosine is deaminated it becomes Uracil which can be recognized from DNA repair machinery and corrected.

Front 12

What is DNA methylation a "hotspot" for mutations?

Back 12

When Cytosine is methylated then undergoes deamination, it looks like Thymine so there is no way to tell if that thymine is normal or mutated

Front 13

What is spontaneous depurination and what types of mutations are causes by it?

Back 13

Removal of a purine base by hydrolysis of glycosidic bonds which produces an apurinic site of DNA (AP)
Mutations:
1. Transition and transversion
2. Base pair deletion
3. DNA strand breaks

Front 14

What is the occurance of:
1. tautomers
2. deamination of cytosine to uracil
3. spontaneous derpurination

Back 14

1. 10^-4
2. 10^-7
3. 10^-4- - 10^-5

Front 15

What are two 'hotspots' for base changes or insertions?

Back 15

methylation of cytosine and single nucleotide runs

Front 16

What type of mutations can be caused by deamination by HNO2?

Back 16

Transitions:
Cytosine is mutated to uracil so instead of a C-G, you get U-A
Adenine is mutated to hypoxathine so stead of a A-T, you get a H-C

Front 17

What are examples of intercalating agents and how do they cause mutations?

Back 17

Ethidium bromide, acridine dyes insert inbetween bases and 'stretch" the DNA helix which can cause insertions

Front 18

What are examples of alkylating agents and what mutations do they cause?

Back 18

ex) DMSO, Alfatoxin
They add methyl or ethyl groups which causes Transitions by alkylating G which will pair with T instead of C

Front 19

What are the types of DNA damage produces by the generation of free radicals like ROS and RNS?

Back 19

OH especially does damage:
OH generates 8-hydroxyguanine which causes transversions by pairing A instead of C and OH causes DNA strand breaks which can result in deletion of one ore more base pairs when the strand breaks are repaired by non-homologous end joining

Front 20

What mutations does cigarette smoke cause?

Back 20

It adds bulky chemical groups to DNA which G bases and causes the double helix to distort

Front 21

What mutations are caused by exposure to UV light?

Back 21

Thymine dimers which distorts the DNA helix and impairs replication and transcription

Front 22

What spontaneous causes and induced causes create base pair substitution: transitions and transversions?

Back 22

spontaneous= tautomerization, polymerase error, deamination, depurination
induced= deamination by HNO2, depurination, free radicals

Front 23

What spontaneous causes and induced causes create insertions?

Back 23

spontaneous= slipped mispairing, triplet repeats
induced= intercalating agents

Front 24

What spontaneous causes and induced causes creates DNA strand breaks and deletion?

Back 24

spontaneous=depurination
induced=free radicals, depurination by alkylating agents

Front 25

What induced mutation causes creates distortion of the double helix?

Back 25

exposure to UV to form thymine dimers, addition of bulky chemical groups (aromatic hydrocarbons)

Front 26

What are 2 examples of direct reversal of DNA damage?

Back 26

1. removal of methyl or ethyl group at O-6 from alkylated guanine by the enzyme o6-methylguanine methyltransferase
2. joining of the non-homologous end of double stranded breaks by ligase

Front 27

Why can direct repair of DNA strand break cause deletions?

Back 27

Damaged bases at breaks are lost and not replaced when the strands get put back together

Front 28

Describe mismatch repairs in prokaryotes and eukaryotes.

Back 28

The newly synthesized DNA is recognized. Prokaryotes do not have methylated DNA on the daughter strand. In eukaryotes the lagging strand is recognized by gaps between okazaki fragments and the leading strand is recognized by its 3' growing end
In prokaryotes MutS recognizes mismatched pairs and in eukaroytes hMSH2 recognizes mismatched pairs. MutL (prokaryotes) or hMLH1(humans) recruit Mut H to excise a chunk of oligonucleotides around the mismatch with the help of helicase and exonuclease
in prokaryotes DNA polymerase I fills in the gaps and DNA polymerase B in human does that same job. DNA ligase seals the strand

Front 29

Which DNA repair happens during replication and which happens after replication?

Back 29

Mismatch repair happens during replication and base excision repair happens after replication

Front 30

Describe base excision repair.

Back 30

DNA glycosylase scans along DNA and detects incorrect base pairs and cleaves the N-glycosidic bond to generate an AP site. AP endonuclease breaks the DNA backbone by cleaving the phosphodiester bond and deoxyribosephosphodiesterase removes deoxyribose and reates a free 3' OH and 5' Pi. DNA polymerase B fill in the gap and DNA ligase seals the DNA

Front 31

What are examples of damages bases that are repaired by base excision repair?

Back 31

deamination of A to form hypoxathine
oxidation of guanine to form 8-hydroxyguanine
deamination of C to U

Front 32

Describe how a thymine dimer is removed by nucleotide excision repair.

Back 32

This recognizes 'lesions' that cause distortion
1. excinuclease complex contain proteins that: a)recognize specific types of DNA damage or 'lesions' b)DNA helicase that unwinds the DNA strand sin the damages region c) 5'-endonucleaes and 3'-endonucleases cleave and excise the strand on either side of the damaged DNA
2. DNA polymerase B fills the gap
3. DNA ligase seals the DNA strand

Front 33

Describe the mechanism of transcription-coupled repair.

Back 33

This mechanism is a type of nucleotide excise repair for actively transcribed genes.
1. RNA polymerase stalls when it encounters a thymine dimer
2. CSA and CSB proteins recognize the stalled RNA polymerase and displaces it to terminate transcription
3. CSA and CSB recruit excinuclease complex to undergo nucleotide excision repair

Front 34

What types of DNA damage are repaired by recombinatorial repair?

Back 34

DNA double stranded breaks by homologous (not like non-homologous joining of ends by DNA ligase) so it restores it to the original sequence

Front 35

What DNA repair mechanism is defective in xeroderm pigmentosum?

Back 35

nucleotide excision repair-components f the exinculease complex

Front 36

What DNA repair mechanism is defective in herediatry nonpolyposis colorectal cancer?

Back 36

mutation in mismatch repair is ~15% of colon cancers

Front 37

What DNA repair mechanism is defective in cockayne's syndrome?

Back 37

Transcription-coupled repair- espcially CSB and CSA which causes impaired growth, neurological development, premature aging, and sensitivity to sunlight

Front 38

What DNA repair mechanism is defective in Ataxia telangiectasia?

Back 38

ATM gene-protein kinase involved in damage control during cell cycle so ATM can't detect DNA breaks so p53 levels don't increase to stop the cell cycle

Front 39

What DNA repair mechanisms is defective in hereditary breast cancer?

Back 39

BRCA1 and BRCA2 that code for recombinatorial repair

Front 40

What can direct reversal of DNA damage repair and what are the key components to this mechanism?

Back 40

Alkylation of G at O8 and DNA strand breaks

O6-methytransferase or 06 ethyltransferase

Front 41

How can base pairs that are mismatched during DNA replication be repaired and with what key components?

Back 41

Mismatch repair

MutS and MutL in prokaryotes
hMSH2 and hMLH1 in humans

Front 42

How can a damaged or mutated single base be repaired and with what key components?

Back 42

Base excision repair

DNA glycosylases
AP Endonuclease

Front 43

What mutations do nucleotide excision repair fix and with what key components?

Back 43

Distortion or lesions of the double helix

excinuclease complex

Front 44

What repair mechanism is needed when there is damage in the template DNA that stalls the RNA polymerase and what are the key components to this mechanism?

Back 44

transcription-coupled repair

CSB and CSA
excinuclease complex

Front 45

What does recombinatorial repairs fix and what is the key component?

Back 45

DNA double-strand breaks

Rad51